DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
Claims 3-4, 6-7, 11, and 13-20 have been amended as requested in the amendment filed on 19 December 2025. Following the amendment, claims 1-20 are pending in the instant application.
Claims 4, 11, and 14-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Claims 1-3, 5-10, and 12-13 are examined upon their merits
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 9 January 2026 and 4 March 2026 were filed after the mailing date of the Non-Final mailed on 19 September 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Rejections:
The rejection of Claims 1-3, 5-10, and 12-13 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn. Applicant has provided evidence that Protein Arginine Deiminase and Peptidyl Arginine Deiminase are used interchangeably in the art and, although the correct gene abbreviation for Peptidyl Arginine Deiminase is PADI (see evidence attached to previous Office action), the abbreviation PAD is also known in the literature.
Claim Rejections - 35 USC § 102 (Maintained)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 5-10, and 12-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Seaman et al., Autoimmunity Reviews 15 (2016) 776–780.
On pages 9-11 of Remarks filed 19 December 2025, Applicant traverses the rejection on the following grounds. Applicant asserts that the Examiner has failed to teach the limitation “wherein the at least one PAD protein comprises (i) PAD1 or an antigenic fragment thereof, or (ii) PAD1 or an antigenic fragment thereof and PAD4 or an antigenic fragment thereof” (pg. 9). Applicant argues the PAD3 disclosed in the Seaman prior art does not demonstrate significant antigenic fragment alignment with PAD1 of the claim. Applicant states, the first fragment identified in the pBLAST alignment provided in the previous Office action has 10 out of 20 amino acids that are different from PAD1. Applicant states, “None of these fragments, namely residues 211-230, 271-290, 601-640, are identical to an antigenic fragment of PAD1”.
This is not persuasive to overcome the rejection because specific antigenic fragments are not required by instant claims 1-3, 5-10, and 12-13. The antigenic fragments defined by Applicant in Remarks (“211-230, 271-290, 601-640”) do not appear in the claims. Further, the instant specification fails to provide an explicit definition of the epitopes within the claimed PAD1 or PAD4 that are considered antigenic; the specification merely states: “[0029] In some embodiments, the antigenic fragment comprises from 6-120 …amino acid residues”. The art prior to the filing date of the application teaches antigenic fragments vary in size “but a grouping of the order of six amino acids, contiguous or not, is regarded as a typical number” (as evidenced by Hebbes et al., Mol. Immunol, 26(9): 865-73, September 1989; Abstract). Thus, for purposes of applying prior art, a size of 6 amino acids, which is consistent with both the art at the time of filing and the specification, will be taken as defining an “antigenic fragment”. This does not constitute a new ground of rejection; the Hebbes reference is cited only as evidence in response to Applicant’s arguments.
Given this definition, the prior art still anticipates the method of the instant claim because the Seaman et al. prior art teaches methods comprising contacting a biological sample from persons having Rheumatoid Arthritis (RA) (see Abstract, Methods section) with at least one peptidyl arginine deiminase protein or antigenic fragment thereof. Specifically, the prior art discloses the antigenic fragments comprising epitopes of residues 211-230, 271-290, 601-640 of peptidyl arginine deiminase protein-3 (see Figure 3) are contacted with the samples. The pBLAST alignment provided in the previous Office action is reproduced below depicting the alignment between PADI3, as taught by Seaman et al., and PADI1 of the instant claims. One can see that at least six amino acids are identical within each of the epitopes taught by the prior art (residues 211-230, 271-290, 601-640 are highlighted yellow) and encompassed by the claims.
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Therefore, the Examiner maintains that the prior art teaches the method comprising PADI1 or an antigenic fragment thereof. Additionally, the prior art teaches these same autoantibodies react with PADI4 (Abstract, Background). Lastly, the prior art correlates the presence of Anti-PADI antibodies with joint erosion score (JES), Total Sharp Score (TSS) and Joint Space Narrowing Score (JSNS). Thus, the prior art anticipates (a) contacting a biological sample from a subject having or suspected of having RA (rheumatoid arthritis) with at least one peptidyl arginine deiminase (PAD) protein or an antigenic fragment thereof, and (b) detecting the presence of an autoantibody reactive with the at least one PAD protein or an antigenic fragment thereof, wherein the presence of the autoantibody is indicative of RA or severity of RA; and, wherein the at least one PAD protein comprises (ii) PAD1 or an antigenic fragment thereof, or (ii) PAD4 or an antigenic fragment thereof and PAD4 or an antigenic fragment thereof.
Regarding amended claim 6, the Seaman et al. prior art discloses detecting comprises a chemiluminescent immunoassay (CIA) (pg. 777, at bullet 2, Methods, third paragraph), which anticipates part (a) of the claim. Additionally, the methods of Seaman et al. utilizes biotin-containing antigenic fragments of PAD peptides in a streptavidin ELISA method (pg. 777, at bullet 2, section titled Epitope analysis). The prior art also teaches a QUANTA Flash assay in which “the relative light units (RLUs) are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which in turn is proportional to the amount of anti-PAD3 antibodies bound to the antigen on the beads” (pg. 777, second to last paragraph). This teaches “the detection probe binds to the autoantibody” as recited in part (b)(i) of the amended claim.
Regarding amended claim 7, the Seaman et al. prior art teaches a QUANTA Flash assay in which “the relative light units (RLUs) are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which in turn is proportional to the amount of anti-PAD3 antibodies bound to the antigen on the beads” (pg. 777, second to last paragraph). This teaches “(b) detecting by performing at least one of (i) or (ii) as follows, where:(i) detecting comprises detecting a presence of an autoantibody reactive with the at least one PAD protein or an antigenic fragment thereof, wherein the presence of the autoantibody is indicative of disease progression” as recited in amended part (b)(i) of the claim. Further, Seaman et al. disclose there is an excellent correlation between the detection of anti-PAD antibodies and median joint erosion score (JES) of the 39 patients correlated with the presence of anti-PAD antibody (See Fig. 2). The authors report, when data derived from patients with high levels of anti-PAD antibodies were analyzed, a strong correlation between Total Sharp Score (TSS) and the antibody levels could be found (pg. 778, at bullet 3, Results). Therefore, since joint erosion is an indication of RA disease progression, then the method of the prior art anticipates a method “wherein the presence of the autoantibody is indicative of disease progression” as required by the instant claim.
Regarding amended claim 13, the Seaman et al. prior art discloses a method wherein the detecting comprises at least one of (a) or (b) as follows, where:(a) detecting comprises performing an immunoassay, wherein the immunoassay is a chemiluminescent immunoassay (CIA) (see pg. 777, Methods, Patient Samples). The prior art further teaches detecting comprises contacting the autoantibody bound to the at least one PAD protein or antigenic fragment thereof with a detection probe, wherein detecting using the detection probe comprises at least one of (i), (ii), or (iii) as follows, where:(i) the detection probe binds to the autoantibody. This is taught by the QUANTA Flash CIA assay in which recombinant PAD protein is coated onto paramagnetic beads and the relative light units (RLUs) are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which in turn is proportional to the amount of anti-PAD3 antibodies bound to the antigen on the beads. (pg. 777, at bullet 2, Methods, third paragraph).
For all of these reasons, the methods of the invention fail to distinguish over the methods disclosed in the prior art, and Claims 1-3, 5-10, and 12-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Seaman et al., Autoimmunity Reviews 15 (2016) 776–780.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5-10, and 12-13 stand as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 70-75 of copending Application No. 19/184,462 (reference application) in view of Seaman et al., Autoimmunity Reviews 15 (2016) 776–780, and the pBLAST alignment between the instantly elected PADI1 and PADI4 (above).
On page 11 of Remarks filed 19 December 2025, Applicant argues that claim 70 requires “wherein the detection probe comprises: (i) an antibody or functional fragment thereof capable of binding to anti-PAD4 IgA; or (ii) an antibody or functional fragment thereof capable of binding to anti-PAD4 IgG.”
This is not persuasive because the limitations of the reference claim fall within the metes and bounds of the generic “detecting a presence of an autoantibody reactive with the at least one PAD protein” recited in the instant claim. Both the reference claims and the instant claims have open-ended language (“comprising”) that does not exclude additional elements such as antibodies capable of binding to the auto-antibodies. The rejection is maintained.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M..
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/STACEY N MACFARLANE/Examiner, Art Unit 1675